Unknown,Transcriptomics,Genomics,Proteomics

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Temporal changes of gene expression in rat kidney and lung, and the effect of prior growth inhibition on these changes

ABSTRACT: Temporal changes of gene expression from 1-wk- to 5-wk-old rat in kidney and lung, and the effect of prior growth inhibition on these genetic changes. In mammals, body growth is rapid in early life but decelerates with age. Somatic growth deceleration is caused by a gradual decline in cell proliferation that occurs simultaneously in many different organs, but is not caused by a hormonal mechanism. We hypothesize that growth deceleration is driven by a postnatal genetic program that occurs coordinately in multiple organs. Using microarrays, we investigated the changes of gene expression that occur with age in kidney and lung as growth slows down, and also investigated whether these changes were growth-driven, by asking whether prior delay of postnatal growth caused by malnutrition (tryptophan deficiency) would also delay these genetic changes. To compare gene expression between fast-growing animals and more slowly growing animals, we extracted total mRNA from kidney and lung in 1-wk-old and 5-wk-old mice (5 animals each). Then, to investigate the effect of prior growth on these genetic changes, we also extracted total mRNA from kidney and lung in 5-wk-old mice that received a tryptophan-deficient diet from birth to 4wk of age.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Julian Lui

PROVIDER: E-GEOD-16792 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.

Lui Julian C JC Forcinito Patricia P Chang Maria M Chen Weiping W Barnes Kevin M KM Baron Jeffrey J

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20100406 8

Children grow, but adults do not. The cessation of growth in multiple organs is the end result of a progressive decline in cell proliferation beginning in early life. The mechanisms responsible for this growth deceleration are largely unknown. Using expression microarray and real-time PCR, we identified a common program of gene expression in lung, kidney, and liver during growth deceleration in juvenile rats. Gene ontology analyses and siRNA-mediated knockdown in vitro indicated that many of the ...[more]

PMID: 20371622

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Project description:During early postnatal life, extensive changes in gene expression occur concomitantly in multiple major organs, indicating the existence of a common core developmental genetic program. This program includes hundreds of growth-promoting genes that are downregulated with age in liver, kidney, lung, and heart, and there is evidence that this component of the program drives the widespread decline in cell proliferation that occurs in juvenile life, as organs approach adult sizes. To investigate epigenetic changes that might orchestrate this program, we performed chromatin immunoprecipitation-promoter tiling array to assess temporal changes in histone H3K4 and H3K27 trimethylation (me3) at promoter regions throughout the genome in kidney and lung, comparing 1- to 4-wk-old mice. We found extensive genome-wide shifts in H3K4me3 and H3K27me3 occurring with age in both kidney and lung. The number of genes with concordant changes in the two organs was far greater than expected by chance. Temporal changes in H3K4me3 showed a strong, positive association with changes in gene expression, assessed by microarray, whereas changes in H3K27me3 showed a negative association. Gene ontology analysis indicated that shifts in specific histone methylation marks were associated with specific developmental functions. Of particular interest, genes with decreases in H3K4me3 with age in both organs were strongly implicated in cell cycle and cell proliferation functions. Taken together, the findings suggest that the common core developmental program of gene expression which occurs in multiple organs during juvenile life is associated with a common core developmental program of histone methylation. In particular, declining H3K4me3 is strongly associated with gene downregulation and occurs in the promoter regions of many growth-regulating genes, suggesting that this change in histone methylation may contribute to the component of the genetic program that drives juvenile body growth deceleration. Tissues samples were collect from Lung (1 and 4 week old) and Kindey (1 and 4 week old) respectively with four biological replications of mice that were collected, frozen in liquid nitrogen, and stored at -70 °C

Project description:Microarray analysis of male and female CD-1 mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the pre-pubertal period to young adulthood. A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p < E-76) in the set of genes positively regulated by the liver transcription factor HNF4M-NM-1, as determined in a liver-specific HNF4M-NM-1 knockout mouse model, while genes down regulated during this developmental period showed significant enrichment (p < E-65) for negative regulation by HNF4M-NM-1. Significant enrichment of the developmentally regulated genes in genes subject to positive and negative regulation by pituitary hormone was also observed. Nine sex-specific transcription factors showed pubertal changes in expression and may contribute to the developmental changes that onset after 3-4 wk. Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver. Liver RNA isolated from the following six groups of CD-1 mice was used in the present study: 3 wk old male (M) mice (n = 10; 5 per each pool) and female (F) mice (n = 10; 5 per each pool); 4 wk old male mice (n = 12; 6 per each pool) and female mice (n = 12; 6 per each pool); 8 wk old male mice (n = 12; 6 per each pool) and female mice (n = 12; 6 per each pool). These RNA pools were used in seven separate sets of competitive hybridization experiments: 1) 3 wk M vs. 3 wk F; 2) 4 wk M vs. 4 wk F; 3) 8 wk M vs. 8 wk F; 4) 3 wk M vs. 8 wk M; 5) 4 wk M vs. 8 wk M; 6) 3 wk F vs. 8 wk F; 7) 4 wk F vs. 8 wk F. Fluorescent labeling of RNA and hybridization of the Alexa 555-labeled (green) and Alexa 647-labeled (red) aRNA samples to Agilent Mouse Gene Expression 4x44k v2 microarrays (Agilent Technology, Palo Alto, CA; catalog # G4846A-026655) were carried out, with dye swapping for each of the seven hybridization experiments to eliminate dye bias. Two microarrays, one for each mixed cDNA sample, were hybridized for each of the seven fluorescent reverse pairs, giving a total of 14 microarrays.

Dataset Information

Temporal changes of gene expression in rat kidney and lung, and the effect of prior growth inhibition on these changes

Publications

Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.

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